1- azabicyclo butanes

A variety of carboxylate activating groups convert certain aziridine carboxylates (307) into 3-halogenoazetidin-2-ones (309). The reaction is stereospecific and is believed to proceed via a l-azabicyclo[1.1.0]butan-2-one cation (74JOC902). 

Synthesis and chemistry of substituted l-azabicyclo[1.1.0]butanes 97SL1029. Synthesis of aziridines via stereoselective reactions with imines 99PAC1033. 

Marchand and co-workers reported a synthetic route to TNAZ (18) involving a novel electrophilic addition of NO+ NO2 across the highly strained C(3)-N bond of 3-(bromomethyl)-l-azabicyclo[1.1.0]butane (21), the latter prepared as a nonisolatable intermediate from the reaction of the bromide salt of tris(bromomethyl)methylamine (20) with aqueous sodium hydroxide under reduced pressure. The product of this reaction, A-nitroso-3-bromomethyl-3-nitroazetidine (22), is formed in 10% yield but is also accompanied by A-nitroso-3-bromomethyl-3-hydroxyazetidine as a by-product. Isolation of (22) from this mixture, followed by treatment with a solution of nitric acid in trifluoroacetic anhydride, leads to nitrolysis of the ferf-butyl group and yields (23). Treatment of (23) with sodium bicarbonate and sodium iodide in DMSO leads to hydrolysis of the bromomethyl group and the formation of (24). The synthesis of TNAZ (18) is completed by deformylation of (24), followed by oxidative nitration, both processes achieved in one pot with an alkaline solution of sodium nitrite, potassium ferricyanide and sodium persulfate. This route to TNAZ gives a low overall yield and is not suitable for large scale manufacture. 

The synthesis of TNAZ (18) via the electrophilic addition of NO+NO2 across the C(3)-N bond of l-azabicyclo[1.1.0]butane (26) was found to be very low yielding ( 1 %) and impractical. Nagao and workers reported a similar synthesis of TNAZ via this route but the overall yield was low. 

Funke has observed an interesting reaction of l-azabicyclo[ 1.1.01-butane derivative (115) with DMAD in which an azetidine derivative (117) is formed, presumably through the intermediate 116 [Eq. (19)]. 

A convenient, one-pot, two-step synthesis of l-azabicyclo[1.1.0]butane (5, R = H) from f -chlorosuccinimide is reported and its application to the synthesis of 133-tnnitroazetidine (TNAZ) is discussed <98SC3949>. Another novel and efficient synthesis of 1-aza-bicyclo[1.1.0]butane (5, R = H) and its derivatives is from 23-dibromopropylamine. The bicyclic 5 (R = H) is also useful in the synthesis of the pendant group of a ip-methylcarbapenem antibiotic <99TL3761>. The reaction of 5 (R = Et and Ph) with tosyl chloride and tosyl azide are described <98T15127,99H131>. 

Azabicyclo[l,l,0]butane (1) with DMAD gave the azetidine 3 presumably via the intermediate 2.59a... 

Azabicyclo[1.1.0]butanes serve as a precursor for various N-substituted azetidines. A THF solution of 1-azabi-cyclo[1.1.0]butane, obtained from 2,3-dibromopropanamine hydrobromide, yielded azetidine derivatives on treatment with various reagents such as HCl-EtOH, HBr-ClC02Et, Ts20, HC02H (2.7N) HCl-MeOH, or Ac20-HCl... 

Although a considerable number of 1-azirines have been prepared in a very short time, discovery of new and refinement of old synthetic techniques are clearly needed. Finally, the 1-azirine ring system is potentially a very valuable starting point for the preparation of new and unusual heterocyclic compounds. Already a number of very interesting aziridines have been prepared and 1-azirines were key intermediates for the preparation of the l-azabicyclo[2.1.0]pentane and l-azabicyclo[1.1.0]butane ring systems. 

Photolysis of an alkyl azidoacetate in the presence of 1-methyl- or 1,3,3-trimethyl-cyclopropenes may be explained in terms of an addition of ethoxycarbonylnitrene to the double bond to produce a 2-azabicyclo[1.1.0]butane, but this rearranges under the reaction conditions to the azadiene, although only in low yield 214,215 ... 

The photolysis of l-azido-2-phenylprop-2-ene (132) yielded 3-phenyl-l-azabicyclo[ 1,1,0]butane (133), contaminated with theimine 134, probably via an intramolecular addition of the allylic nitrene... 

The addition of alkoxycarbonylnitrenes to trisubstituted cyclopropenes has been reported to give 2-azabicyclo[1.1.0]butanes 1, which rearrange to a,)S-unsaturated imines in low yield. 

The diene arises through the diazo compound 4 via a retro-[3 -f 2] reaction and diazo compounds of this type have been detected or isolated in several photolyses of 2,3-di-azabicyclo[3.1.0]hex-2-enes. The workup procedure for this particular reaction involves selective removal of the diene by ozonolysis, a chemical method of separating the products which may have applications in related systems since chromatography often proves difficult. In some cases, the intermediate diazabicyclohexenes also prove very sensitive and difficult to handle, rearranging to pyridazines under the influence of acid, base " or light and sometimes, as in the synthesis of methyl 4,4-dimethyl-l,3-diphenylbicyclo[1.1.0]butane-2-carboxyl-... 

Addition of chlorosulfonyl isocyanate to bicyclo[l. 1,0]butanes proceeds rapidly to afford mainly 3-azabicyclo[3.1.0]hexan-2-ones 30. The course of the reaction is believed to involve initial SE2-like attack at the less hindered bridgehead carbon atom followed by cyclobutyl to cyclo-propylmethyl carbenium ion rearrangement or conformational ring inversion, and collapse of the zwitterion. 

Photolysis of methoxycarbonyl azide in the presence of cyclopropenes gives imines, in reactions which are thought to involve the formation and rearrangement of 2-azabicyclo[1.1.0]butanes, e.g. reaction of 2, and 4. ... 

The reaction of 3-substituted 1,2-diphenylcyclopropenes with 4-phenyl-4//-l,2,4-triazole-3,5-dione gave urazoles, possibly via the formation of a spiro[2-azabicyclo[1.1.0]butane-2,T-l,2,4-triazole] and subsequent ring opening. 

Synthesis of l-azabicyclo[1.1.0]butane, which contains both a four-membered and two three-membered nitrogen-containing rings ( ), follows the general route described above. As one would anticipate, ringopening reactions, one of which is illustrated, lead to products with an azetidine unit, rather than an aziridine unit. 

The spectrum of 3-phenyl-l-azabicyclo[l,l,0]butane (47), analysed chiefly by studying the C-satellites, and the spectrum of a deuterium derivative, proves the structure of the compound. 

The sulphur-substituted azabicyclo[1.1.0]butane sulphones and sulphoxides (91) are readily available via reaction of the lithium... 

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